Schizophrenic disorders (inclusively, given the current nosological framework, this may be schizoaffective disorder, schizophreniform disorder, and the subtypes of schizophrenia), a type of psychotic disorder, are complicated psychiatric illnesses with protean behavioral manifestations. These disorders are characterized by the onset of hallucinations, delusional processing, behavioral changes, mood instability, cognitive impairments, and disorganized thinking. Affected individuals typically start showing clinical signs in adolescence and early adulthood. These signs and symptoms are typically experienced and/or demonstrated for life and usually have a profound impact on daily functioning.
Males have been shown statistically to have an earlier onset than females. Clinically, earlier onset tends to result in a more intractable, treatment resistant prognosis. It is also apparent that there is genetic loading for these disorders as it noted epidemiologically that there is familial clustering. While the exact genetic loci and mechanistic underpinnings are not fully understood at this time, it is known from twin studies that monozygotic twins have a concordance rate above 40% for the disorder. Moreover, while there are clearly non-genetic factors accounting for schizophrenic disorders as well, these factors are also not fully delineated at this time.
Current efforts to understand schizophrenia on a neurotransmitter/molecular level have focused on the observed alterations in glutamate and dopamine (glutamatergic and dopaminergic hypotheses). Imaging technologies such as functional magnetic resonance imaging (fMRI) have shown morphologic brain changes that demonstrate the significant and global loss of gray matter in neocortical regions. It is likely, based upon other studies that there are subcortical losses, as well. Current evidence may support the proposition that the severity of schizophrenic disorders increases with greater gray matter volumetric losses. Additionally, it is noted that cortical changes in schizophrenics include a reduced number and/or functionality of interneurons and thus a dysregulation of excitatory neurons. (Benes F M, Berretta S. GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 2001 July; 25(1):1-27; Lodge D J, Behrens M M, Grace A A. A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci, 2009 Feb. 25; 29(8):2344-2354; Spencer K M, Nestor P G, Niznikiewicz M A, Salisbury D F, Shenton M E, McCarley R W. Abnormal neural synchrony in schizophrenia. J Neurosci., 2003 Aug. 13; 23(19):7407-11).
Epidemiological data indicate that schizophrenic disorders are endemic globally in all human populations and have a prevalence of approximately 1% worldwide. Furthermore, when combining the prevalence of other psychotic disorders such as bipolar disorder type 1, unipolar depression with psychosis, and delusional disorders with schizophrenic disorders, a total worldwide prevalence of approximately 3% is reached.
Schizophrenic patients present clinicians with a cloud of symptom clusters and idiosyncratic behaviors. Often, patients have co-morbid anxiety disorders such as OCD or affective disorders such as depression. It can be quite difficult to accurately collect the pertinent data that would aid in diagnosis or demonstrate improvement with a given treatment plan. Despite these diagnostic difficulties, it has become apparent that a significant proportion of these patients have previously unrecognized catatonic features intertwined with psychotic features. Indeed, it may be catatonic features that largely contribute to their so-called treatment resistance. These features are usually chronically present, though some individuals have a dynamic, episodic presentation. Indeed, some patients seem to manifest catatonic features only when fully decompensated due to poor medication adherence.
The treatment for psychotic disorders is primarily pharmacologically based. Medication treatment plans include antipsychotics mood stabilizers, antidepressants, and sedative/hypnotics. Of the aforementioned categories, antipsychotics and mood stabilizers are the primary pharmacological interventions. These classes of medications are often used in various combinations and titrated to various dosages based upon observed clinical effect. Schizophrenic disorders are often less responsive to treatment than other psychotic disorders such as Bipolar disorder type 1. While some individuals can show a good response in that they have remission of the symptoms of psychosis, a significant proportion of those receiving treatment are moderate, marginal, or non-responders. Indeed, the literature notes that from 20 to 60% of individuals with schizophrenic disorders are defined as treatment resistant.
Moreover, it is additionally noted that individuals suffering from other neurological disorders including, for example, Alzheimer's type dementia and severe forms of autism may have a poor response to conventional treatment due to the co-morbidity of catatonic features. Thus, as is believed for psychotic disorders, the reduction or elimination of the catatonic features may enable clinicians to improve treatment response in a number of other psychiatric/neurological disorders. Herein, a treatment for catatonic features in individuals suffering therefrom alone or in addition to other psychotic and/or neurological disorders is disclosed.